Experimental Epileptogenesis in a Cell Culture Model of Primary Neurons from Rat Brain: A Temporal Multi-Scale Study

Understanding seizure development requires an integrated knowledge of different scales of organization of epileptic networks. We developed a model of “epilepsy-in-a-dish” based on dissociated primary neuronal cells from neonatal rat hippocampus. We demonstrate how a single application of glutamate s...

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Autores principales:	Janos Jablonski, Lucas Hoffmann, Ingmar Blümcke, Anna Fejtová, Steffen Uebe, Arif B. Ekici, Vadym Gnatkovsky, Katja Kobow
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	epilepsy in vitro epigenetic DNA methylation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/42b2113b33bc461cab26aec03e6c6836
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spelling	oai:doaj.org-article:42b2113b33bc461cab26aec03e6c68362021-11-25T17:10:18ZExperimental Epileptogenesis in a Cell Culture Model of Primary Neurons from Rat Brain: A Temporal Multi-Scale Study10.3390/cells101130042073-4409https://doaj.org/article/42b2113b33bc461cab26aec03e6c68362021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3004https://doaj.org/toc/2073-4409Understanding seizure development requires an integrated knowledge of different scales of organization of epileptic networks. We developed a model of “epilepsy-in-a-dish” based on dissociated primary neuronal cells from neonatal rat hippocampus. We demonstrate how a single application of glutamate stimulated neurons to generate spontaneous synchronous spiking activity with further progression into spontaneous seizure-like events after a distinct latency period. By computational analysis, we compared the observed neuronal activity in vitro with intracranial electroencephalography (EEG) data recorded from epilepsy patients and identified strong similarities, including a related sequence of events with defined onset, progression, and termination. Next, a link between the neurophysiological changes with network composition and cellular structure down to molecular changes was established. Temporal development of epileptiform network activity correlated with increased neurite outgrowth and altered branching, increased ratio of glutamatergic over GABAergic synapses, and loss of calbindin-positive interneurons, as well as genome-wide alterations in DNA methylation. Differentially methylated genes were engaged in various cellular activities related to cellular structure, intracellular signaling, and regulation of gene expression. Our data provide evidence that a single short-term excess of glutamate is sufficient to induce a cascade of events covering different scales from molecule- to network-level, all of which jointly contribute to seizure development.Janos JablonskiLucas HoffmannIngmar BlümckeAnna FejtováSteffen UebeArif B. EkiciVadym GnatkovskyKatja KobowMDPI AGarticleepilepsyin vitroepigeneticDNA methylationBiology (General)QH301-705.5ENCells, Vol 10, Iss 3004, p 3004 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	epilepsy in vitro epigenetic DNA methylation Biology (General) QH301-705.5
spellingShingle	epilepsy in vitro epigenetic DNA methylation Biology (General) QH301-705.5 Janos Jablonski Lucas Hoffmann Ingmar Blümcke Anna Fejtová Steffen Uebe Arif B. Ekici Vadym Gnatkovsky Katja Kobow Experimental Epileptogenesis in a Cell Culture Model of Primary Neurons from Rat Brain: A Temporal Multi-Scale Study
description	Understanding seizure development requires an integrated knowledge of different scales of organization of epileptic networks. We developed a model of “epilepsy-in-a-dish” based on dissociated primary neuronal cells from neonatal rat hippocampus. We demonstrate how a single application of glutamate stimulated neurons to generate spontaneous synchronous spiking activity with further progression into spontaneous seizure-like events after a distinct latency period. By computational analysis, we compared the observed neuronal activity in vitro with intracranial electroencephalography (EEG) data recorded from epilepsy patients and identified strong similarities, including a related sequence of events with defined onset, progression, and termination. Next, a link between the neurophysiological changes with network composition and cellular structure down to molecular changes was established. Temporal development of epileptiform network activity correlated with increased neurite outgrowth and altered branching, increased ratio of glutamatergic over GABAergic synapses, and loss of calbindin-positive interneurons, as well as genome-wide alterations in DNA methylation. Differentially methylated genes were engaged in various cellular activities related to cellular structure, intracellular signaling, and regulation of gene expression. Our data provide evidence that a single short-term excess of glutamate is sufficient to induce a cascade of events covering different scales from molecule- to network-level, all of which jointly contribute to seizure development.
format	article
author	Janos Jablonski Lucas Hoffmann Ingmar Blümcke Anna Fejtová Steffen Uebe Arif B. Ekici Vadym Gnatkovsky Katja Kobow
author_facet	Janos Jablonski Lucas Hoffmann Ingmar Blümcke Anna Fejtová Steffen Uebe Arif B. Ekici Vadym Gnatkovsky Katja Kobow
author_sort	Janos Jablonski
title	Experimental Epileptogenesis in a Cell Culture Model of Primary Neurons from Rat Brain: A Temporal Multi-Scale Study
title_short	Experimental Epileptogenesis in a Cell Culture Model of Primary Neurons from Rat Brain: A Temporal Multi-Scale Study
title_full	Experimental Epileptogenesis in a Cell Culture Model of Primary Neurons from Rat Brain: A Temporal Multi-Scale Study
title_fullStr	Experimental Epileptogenesis in a Cell Culture Model of Primary Neurons from Rat Brain: A Temporal Multi-Scale Study
title_full_unstemmed	Experimental Epileptogenesis in a Cell Culture Model of Primary Neurons from Rat Brain: A Temporal Multi-Scale Study
title_sort	experimental epileptogenesis in a cell culture model of primary neurons from rat brain: a temporal multi-scale study
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/42b2113b33bc461cab26aec03e6c6836
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Experimental Epileptogenesis in a Cell Culture Model of Primary Neurons from Rat Brain: A Temporal Multi-Scale Study

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